T helper type 17 (Th17) lymphocytes are characterized by the production of interleukin (IL)-17; these cells are involved in many autoimmune disorders. Th17 cells are also involved in ocular inflammatory diseases, such as uveitis, scleritis, dry eye syndrome, and corneal inflammation (see Kang et al., J. Korean Med. Sci. 26: 938-944, 2011).
Intraocular inflammatory diseases grouped under the term “uveitis” are a major cause of visual loss in industrialized nations. “Uveitis” refers to an intraocular inflammation of the uveal tract, namely, the iris, choroids, and ciliary body. Uveitis is responsible for about 10% of legal blindness in the United States (National Institutes of Health, Interim Report of the Advisory Eye Council Support for Visual Research, U.S. Department of Health Education and Welfare, Washington, D.C., 1976, pp. 20-22). Complications associated with uveitis include posterior synechia, cataract, glaucoma, and retinal edema (Smith et al., Immunol. Cell Biol. 76:497-512, 1998).
Autoimmune uveitis is a sight-threatening disease driven by retina-specific T cells that target the neuroretina of the eye; studies in animal models of experimental autoimmune uveitis (EAU) indicate that Th17 cells are a major effector population. The Th17 response and IL-17A have been associated with host defense as well as with autoimmune diseases in patients and in experimental animal models. IL-17A is recognized as the Th17 signature cytokine, and IL-17A-producing T cells are pathogenic effectors in models of autoimmunity, including experimental autoimmune uveitis (EAU) induced by immunization with the retinal protein IRBP in complete Freund's adjuvant.
Treatment of uveitis often focuses on control of the inflammatory symptoms. In such cases, corticosteroids are often used to suppress inflammation in the eye. Anterior uveitis often responds to local steroid treatment with eye drops. However, drops do not usually provide therapeutic levels of steroids in the posterior part of the eye for the treatment of posterior uveitis or panuveitis. Periocular injections are then indicated. These injections can be given sub-conjunctively or beneath Tenon's capsule.
Systemic treatments with corticosteroids are often used when local injections fail. However, many of the most severe cases of uveitis do not respond to high-dose systemic corticosteroid therapy. In addition, the side effects of such systemic therapies can include hypertension, hyperglycemia, peptic ulceration, Cushingoid features, osteoporosis, growth limitation, myopathy, psychosis, and increased susceptibility to infection, which can be devastating. Finally, many of the local and systemic steroid therapies also have potentially sight-threatening side effects, such as glaucoma, cataract, and susceptibility to eye infection. Newer immunosuppressive agents are being investigated for use in uveitis treatment, such as tacrolimus, sirolimus, and mycophelonate mofetil. However, these drugs also have serious side effects (Anglade and Whitcup, Drugs 49:213-223, 1995). Therefore, there exists a need for new methods to treat inflammatory disease of the eye.